can be detected (Figure 21.2a, b, c), but the most characteristic are antibodies directed against double-stranded deoxyribonucleic acid and antibodies directed against Sm and U1-sn RNP (Figure 21.3).
Pulmonary manifestations of SLE are due to immune complex lung injury. Almost any pulmonary structure can be affected in SLE (Table 21.1).There are other causes of pul- monary injury in SLE, like pneumonias, thromboembolic incidences, and edema due to cardiac failure. All these conditions may cause acute respiratory illness with respiratory insufficiency. Acute course of the disease is also a feature of acute lupus pneumonitis and sometimes diffuse alveolar hemorrhage.
Acute lupus pneumonitis is a clinical syndrome detected in 1–5% of patients with a mortality of 50%. Histopathologically, diffuse alveolar damage and nonspecific intersti- tial pneumonia are revealed. It resembles the clinical course of acute pneumonia. Plain radiograph of the chest shows bilateral or unilateral alveolar infiltrates, sometimes with pleural effusion or atelectasis (Figure 21.4c). As the mortality is extremely high, the aggressive diagnostic and therapeutic approach is recommended. The infectious agents have to be excluded as they are the most frequent cause of lung infiltrates in SLE.
High doses of corticosteroids and immunosuppressive agents (intravenous cyclophos- phamide) are efficient in some cases.
Diffuse alveolar hemorrhage (DAH) is a serious and life-threatening pulmonary com- plication in SLE. It is a rare event, and it occurs in about 2% of patients with a mortal- ity of 50–90%. Women are more frequently affected than men; usually nephritis, nephrotic syndrome, renal failure, and positive anti-DNA antibodies are present.
Histopathologically, acute inflammation and necrosis involving capillaries, arterioles, and small muscular arteries has been described. The dominant symptom is dyspnea, with or without hemoptysis, fever, and anemia. Chest radiograph shows bilateral alveo- lar opacities (Figure 21.4a, b). The reduction of hemoglobin concentrations gives rise to the possibility of pulmonary hemorrhage. The lung lavage fluid becomes macroscopi- cally more bloody during the procedure, and cytologically the hemosiderin-laden macrophages (siderophages) are detected. Bronchoscopy also allows for a search for infectious agents.
High doses of corticosteroids are reported to be effective, but sometimes immuno- suppressive agents have to be introduced. Plasmapheresis should be reserved for patients with multiorgan SLE and severe DAH refractory to corticosteroids and cyclophosphamide.
Chronic forms of interstitial lung disease in SLE are uncommon, although HRCT scan- ning has shown that 30% of the patients have some form of the disease albeit the normal plain radiograph of the chest. Pulmonary function tests were abnormal in about 50% of the patients with abnormal HRCT. Chronic forms of lung disease in SLE present with slowly progressive dyspnea. Histopathological analysis reveals UIP, NSIP, BOOP, or LIP (Figure 21.5). Most investigators believe that there is an evolution from acute to chronic forms of ILD in SLE. Plain chest radiographic (Figure 21.6a, b) and HRCT (Figure 21.6c) 119
Figure 21.1. Butterfly rash on the face of a person with SLE.
Figure 21.2. Fluorescence of the nuclei in the tissue shows the presence of anti-nuclear antibodies (ANA); the fluorescence may be speckled, perinuclear, or homogeneous.
Speckled nuclear fluorescence (on home-made rat liver; objective ×100) cause antibod- ies directed against various target antigens (hn-RNP, U1-RNP, Sm, SS-A, SS-B) (a), perin- uclear fluorescence of the nucleus (on home-made rat liver; objective ×100) cause antibodies directed against nuclear membrane laminins (b), but homogeneous is typical of SLE, though it also occurs in a range of other autoimmune and connective tissue dis- eases. These are antibodies directed against ds-DNA. Homogeneous diffuse fluorescence of the entire nucleus of interphase cells and the chromosomal region in mitotic cells (Hep-2 cells; Euroimmun, Lubeck, Germany; objective ×40) (c).
䉴
Table 21.1. Pleuropulmonary manifestations of systemic lupus erythematosus.
Pleuropulmonary Manifestations Frequency
Parenchymal disease
Usual interstitial pneumonia (UIP) ±
Nonspecific interstitial pneumonia (NSIP) + Bronchiolitis obliterans organizing pneumonia (BOOP) ±
Lymphoid interstitial pneumonia (LIP) ±
Diffuse alveolar damage (DAD) +
Diffuse alveolar hemorrhage (DAH) +
Acute lupus pneumonitis, combination of DAD and NSIP + Airway disease
Upper airway dysfunction +
Bronchiolitis obliterans ±
Bronchiectasis ±
Pleural disease
Pleural effusion +++
Diaphragmatic disease
Diaphragmatic dysfunction +
“Shrinking lung syndrome” ±
Pulmonary vascular disease
Thromboembolic disease +
Vasculitis +
Pulmonary hypertension ++
Miscellaneous
Weakness of respiratory muscles ++
Mediastinal lymphadenopathy +
+++, common; ++, fairly frequent; +, occasional; ±, rare.
Figure 21.3. Antibodies directed against Sm and U1-sn RNP. Typical coarse speckled pattern with nucleolar sparing and occasional slight cytoplasmic staining (Hep-2 cells;
Euroimmun, Lubeck, Germany; objective ×40).
Figure 21.4. The radiological chest analysis in SLE is diverse. Diffuse alveolar hemor- rhage presents as reticular interstitial and focal alveolar pattern in the left lower lobe by plain radiograph (a). HRCT scan of the same patient who presented with hemoptysis reveals centrilobular, perivascular patchy ground-glass pattern with no vessels affected.
This was the only initial manifestation of SLE, which was later confirmed by identifica- tion of positive ANA, anti-dsDNA antibodies, and antibodies directed against Sm (b).
Lupus pneumonitis showing bilateral alveolar pattern (c) is another acute serious event that can be seen in SLE patients.
Figure 21.5. Systemic lupus erythematosus histology shows widening of septa with dense lyphocytoid infiltrates—nonspecific interstitial pneumonia—and accumulation of macrophages in alveolar spaces.
Figure 21.6. Chest radiograph in chronic form of interstitial lung disease in SLE shows bilateral and bibasilar coarse reticular changes most frequently due to usual interstitial pneumonia. This is a radiogram of a female 9 years ago; then changes were mild (a), and they slowly progressed to diffuse reticular pattern (b), and now the HRCT scan reveals the reticular pattern, intralobular thickening, patchy ground-glass opacities, traction bronchiectasis, and architectural distortion, predominantly in the lower lobes. The fibrous pleural changes are seen (c).
findings are almost identical to the finding in IPF. The most common physiological deficit is the reduction in diffusing capacity. Restrictive ventilatory changes are fre- quently detected. Bronchoalveolar lavage is helpful in exclusion of the infections and alveolar hemorrhage, but less in the procedure of evaluation of the SLE lung changes. As pleural effusion is common, the exudate is sometimes analyzed (Figure 21.7). Open lung biopsy is seldom indicated. Treatment of chronic forms of ILD in SLE is poorly evalu- ated. Patients treated with corticosteroids improve in the majority of cases. Improvement with oral methotrexate has been reported.
Serious complications of SLE are antiphospholipid syndrome and pulmonary hyper- tension. Antiphospholipid syndrome occurs as a feature of SLE or as an independent, primary disorder. In 30–40% of patients with SLE, the antiphospholipid antibodies are found. The presence of these antibodies increases 3–4 times the incidence of throm- boembolic events but also the development of thrombotic and nonthrombotic pul- monary hypertension, pulmonary arterial thrombosis, pulmonary microemboli, ARDS, and alveolar hemorrhage. Moderate-intensity warfarin for thromboprophylaxis in patients with antiphospholipid antibodies and previous thrombosis is appropriate, with the target International Normalized Ratio (INR) from 2.0 to 3.0.
Bibliography
1. Santos-Ocampo AS, Mandell BF, Fessler BJ. Alveolar hemorrhage in systemic lupus erythematosus:
Presentation and management. Chest 2000;118(4):1083–1090.
2. Fink SD, Kremer JM. Successful treatment of interstitial lung disease in systemic lupus erythematosus with methotrexate. J Rheumatol 1995;22:967–969.
3. Crestani B. The respiratory system in connective tissue disorders. Allergy 2005;60:715–734.
4. Strange C, Highland K. Interstitial lung disease in the patient who has connective tissue disease. Clin Chest Med 2004;25:549–560.
5. Bankier AA, Kiener HP, Wiesmayr MN, Fleischmanu D, Kontrus M, Herold CJ, Graninger W, Hubsch P. Dis- crete lung involvement in systemic lupus erythematosus: CT assessment. Radiology 1995;196:434–439.
6. Crowther MA, Ginsberg JS, Julian J, Denburg J, Hirtsh J, Douketis J, Laskin C, Fortin P, Anderson D, Kearon C, Clarke A, Geerts W, Forgie M, Green D, Consfantini L, Yacura W, Wilson S, Gent M, Kovacs MJ. A com- parison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003;349:1133–1138.
Figure 21.7. Frequently, pleural effusion is found in patients with SLE. The predominant cells in pleural exudate are lymphocytes, but occasionally LE cells can be found. LE cell (arrow), small lymphocytes, eosinophils, and erythrocytes are seen. Pleural fluid cytol- ogy, original magnification ×400, MGG stain (May-Grünwald-Giemsa).
